269 results about "Co-stimulation" patented technology

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Immunization of human antibody-producing transgenic mice, which have been created using genetic engineering techniques, with AILIM molecule as an antigen resulted in various human monoclonal antibodies capable of binding to AILIM and capable of controlling a variety of biological reactions (for example, cell proliferation, cytokine production, immune cytolysis, cell death, induction of ADCC, etc.) associated with AILIM-mediated costimulatory signal (secondary signal) transduction. Furthermore, it has been revealed that the human monoclonal antibody is effective to treat and prevent various diseases associated with AILIM-mediated costimulatory signal transduction, being capable of inhibiting the onset and/or advancement of the diseases.

The invention relates to a chimeric antigen receptor with stable antigen binding units. The chimeric antigen receptor comprises the extracellular antigen binding units, trans-membrane domains and intracellular co-stimulation signal domains. The antigen binding units can be stably expressed as compared with specific tumor targets and comprise heavy chains and light chains which are connected with one another by hinges of SEQ ID NO.2 (sequence identity number.2) amino acid sequence codes. The invention further relates to cells for expressing the receptor and application of the receptor.

The present invention provides methods and compositions for expanding Treg cells ex vivo or in vivo using one or more conjugates comprising a costimulatory moiety that stimulates at least one of three signals involved in Treg cell development and/or using dendritic cells pulsed with antigens and modified to display TGF-β, or hematopoetic stem cells or bone marrow cells modified to display TGF-β. The methods and compositions are useful, for example, in the treatment and prevention of autoimmune disease, including Type 1 diabetes and in preventing foreign graft rejection, as well as to establish mixed chimerism, induce tolerance to autoantigens, alloantigens or xenoantigens, beta cell regeneration, prevention of foreign graft rejection, and treatment of a genetically inherited hematopoietic disorder.

[Solving means] A thienotriazolodiazepine compound of the following formula (I)

a pharmaceutical agent containing the compound as an active ingredient, and a production intermediate and a production method of the thienotriazolodiazepine compound.

[Effect]Since this compound has an inhibitory action on costimulatory signal from CD28 on T cell, it is useful for the prophylaxis or suppression of rejection reaction in transplantation of organ or bone marrow and the like, and the prophylaxis or treatment of autoimmune diseases or allergic diseases.

The invention discloses a recombined chimeric antigen receptor with a photoinduction element. The chimeric antigen receptor comprises an antigen combining area, a transmembrane structure area, a co-stimulatory signal transduction area and T cell signal transduction area functional structure domains, wherein the photoinduction element is inserted at the N terminal or C terminal of the recombined chimeric antigen receptor or between the functional structure domains. According to the chimeric antigen receptor, photoinduction element LOV2 genes are cloned into plasmids Lenti-EF1alpha-CD19CAR with a molecular cloning method to establish a co-expression vector of the recombined chimeric antigen receptor with the photoinduction element, 293T cells are used for packaging to obtain a lentiviral vector with photoinduction CAR molecules. After the recombined chimeric antigen receptor is expressed in T cells through the lentiviral vector, the damage toxicity of T cells is reversely controlled by LOV2, and an importable approach is provided for improving the safety of CAR-T in treating cancer clinically.

The present disclosure provides a method for enhancing the anti-tumor efficacy of an Fc fusion protein which binds specifically to a target, e.g., a co-inhibitory or co-stimulatory receptor of ligand, on a T cell in a subject afflicted with a cancer or a disease caused by an infectious agent and alters the activity of the immunomodulatory target, thereby potentiating an endogenous immune response against cells of the cancer or the infectious agent, wherein the method comprises selecting, designing or modifying the Fc region of the Fc fusion protein so as to enhance the binding of said Fc region to an activating Fc receptor (FcR). The disclosure also provides an Fc fusion protein produced by said method which has an enhanced ability to potentiate an endogenous immune response against cells of a cancer or an infectious agent in a subject. The disclosure further provides a method for treating a subject which comprises administering to the subject a therapeutically effective amount of an Fc fusion protein, wherein the Fc region of the Fc fusion protein has been selected, designed or modified so as to increase the binding of said Fc region to an activating FcR.

The invention relates to a chimeric antigen receptor (CAR) and application thereof. The CAR comprises BCMA (B-cell maturation antigen) binding structural domains, transmembrane structural domains, oneor a plurality of co-simulation structural domains and intracellular signal transduction structural domains. The BCMA binding structural domains comprise heavy chain complementary determining regionsHCDR 1-3, and amino acid sequences of the HCDR 1-3 are sequentially shown as SEQ ID NO:1-3.

The invention relates to a single chimeric converter for a T-cell signal and application thereof, which belongs to the fields of molecular biology and immunology. Specifically speaking, the single chimeric converter is formed by connection of a polypeptide highly efficiently bonding with immunosuppression molecules on the surfaces of tumor cells and/or tumor matrix cells to a transmembrane domain originated from a high-affinity receptor and an intracellular peptide fragment of a costimulatory signal molecule through a hinge structure. Out-membrane polypeptide receives a signal of the immunosuppression molecules on the surfaces of tumor cells and/or tumor matrix cells and transmits the signal into a cell, a second signal of immune cells is activated through the intracellular peptide fragment of the costimulatory signal molecule, so multiplication capacity of the immune cells and the secretion function of cell factors are enhanced, and the survival time of the activated immune cells is prolonged; thus, side-effects of a tumor immunosuppression microenvironment on adoptive cell therapy effector cells are overcome.

The invention relates to the technical field of adipose mesenchymal stem cells in the technical field of cell therapy, in particular to a method for enhancing an immune regulating function and a migration capacity of adipose mesenchymal stem cells. Primary culture and secondary culture are performed to the adipose mesenchymal stem cells obtained through separation, and then short-time culture is performed by using culture medium containing low-concentration TLR3 activator Poly(I:C). After Poly(I:C) co-stimulation culture is performed, the obtained adipose mesenchymal stem cells with a brand new phenotype have a stronger migration capacity, the levels of secreting cytokine and chemotactic factor are changed and a stronger immunosuppressive function is reflected on the whole.

Method and apparatus for simulating operations of a circuit design that includes high-level components and HDL components. Groups of HDL components are associated with different co-simulation engines. The high-level components of the design are simulated in a high-level modeling system (HLMS), and the HDL components in each group are simulated on the associated co-simulation engine.

The invention relates to a chimeric antigen receptor, nucleic acid encoding the same, cells expressing the chimeric antigen receptor, and application of the chimeric antigen receptor in preparing drugs for treating tumors. The chimeric antigen receptor comprises at least one extracellular structural domain, an optional membrane spanning structural domain and at least one intracellular co-stimulation signal transduction structural domain, wherein the extracellular structural domains involve CD19 antigen recognition binding structural domains. The chimeric antigen receptor has a longer in-vivo survival period after being subjected to humanized transformation, and the complete remission period of a patient can also be prolonged accordingly.

The invention relates to the field of tumor cellular immunotherapy, and in particular relates to a recombinant lentivirus and application thereof. The recombinant lentivirus comprises a chimeric antigen receptor, wherein the chimeric antigen receptor mainly comprises signal peptide, an antigen recognition domain, a transmembrane domain, an intracellular co-stimulation signal transduction domain and a CD3 zeta signal transduction domain which are serially connected; the intracellular co-stimulation signal transduction domain mainly comprises a human TLR2 (Toll Like Receptor 2) intracellular domain. A GPC3 CAT T (Glypican 3 CAT T) cell prepared from the recombinant lentivirus has an intense cell killing effect on liver cancer cells, a Th1 cell factor can be highly expressed, a tumor killing effect caused by non-CAR T (Chimeric Antigen Receptor T) cell can be stimulated to the maximum extent, escape and potential reoccurrence risk of GPC 3-tumor cells can be effectively prevented, the tumor cells can be killed by T cells expressing the chimeric antigen receptor, normal tissue can be slightly damaged, a tumor immunosuppression micro environment can be broken through, and thus a relatively good treatment effect on solid tumor can be achieved.

The invention aims to provide an efficient culture method of CIK cells. The prepared CIK cell has the characteristics of high multiplication speed, large cell quantity, high cell viability, high killing capacity on cancer cells and the like. The efficient culture method mainly characterized in that a culture flask coated with laminin and fibronectin is used for culturing PBMCs (peripheral blood mononuclear cells), and the cells can be in a half-adherence state by means of the absorption effect of the two kinds of protein, accordingly, the cells can be stimulated by various factors, and the two kinds of protein can promote CIK cell multiplication; and with the adoption of an anti-CD28 monoclonal antibody, the co-stimulation signal of a T cell subset in the CIK cells can be stimulated, and the activation of the CIK cells is promoted. So far, a research report on jointly using laminin, fibronectin and the anti-CD28 monoclonal antibody to prepare the CIK cells is absent. The method for increasing the cell number and improving the killing activity by adding the three factors during preparation of the CIK cells is firstly provided.

The invention discloses an anti-EGFRvIII chimeric antigen receptor, an encoding gene, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. The anti-EGFRvIII chimeric antigen receptor comprises CD8 leader chimeric receptor signal peptide, an EGFRvIII single-chain antibody light chain VL, Optimal Linker C, an EGFRvIII single-chain antibody heavy chain VH, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulated factor and a TCR chimeric receptor T cell activating domain which are connected in series. Moreover, the invention discloses an encoding gene of the anti-EGFRvIII chimeric antigen receptor, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. Secretion of cell factors and an in-vitro killing effect of CAR-T cells are obviously improved, and the CAR-T cells have an outstanding clinical treatment effect.

The invention provides a magnetism, pH (potential of hydrogen) and temperature co-stimulation response hydrogel pre-radiation synthetic method, belongs to the technical field of nuclear biology, and solves the technical problems of low existing nano-composite hydrogel environment stimulation response rate and the like. The synthetic method includes the steps: 1) injecting temperature sensitive monomer solution into PE (polyethylene) sealing bag, leading in N2, and performing pre-radiation cross-linking reaction under electron beams; 2) placing macromolecule irradiation sensitizing agents, natural polysaccharide, pH conditioning agents, magnetic nano-particles and distilled water or deionized water into a bottle, and the heating the bottle; 3) slowly adding a mixed solution system acquiredin the step 2) into the temperature sensitive monomer solution acquired in the step 1), performing uniformly ultrasonic stirring, and leading in the N2; 4) injecting the mixed system acquired in the step 3) into the PE sealing bag, and performing radiation cross-linking reaction under electron beams again. The method has the advantages that the comprehensive performances of nano-composite hydrogelare optimized and the like.

The invention discloses a pressure-electricity co-stimulation cell culture device. The device comprises a cell incubator, a cell culture cavity fixing device, a cell culture cavity, a transmission device, a stepper motor and a signal generator, wherein the incubator is provided with a pore canal communicated with the outside; the cell culture cavity is fixed on the cell culture cavity fixing device; the cell culture cavity comprises a connecting rod, an upper cavity, a pressure head, a cell-material composite culture and a lower cavity; the upper cavity is fixed on a transmission plate of thetransmission device and is connected with the stepper motor through a sliding screw rod; the lower cavity is fixed in a circular groove of a base of the cell culture cavity fixing device; the cell-material composite culture is arranged in the lower cavity; and the signal generator is connected with a metal electrode in the cell culture cavity. The device has the advantages of overcoming the defect that a physical microenvironment for in vivo cells under which pressure stimulation and electricity stimulation coexist cannot be simulated by the conventional method, establishing a pressure-electricity co-stimulation cell culture method and promoting the development of cells, a tissue culture method and a relevant tissue engineering reactor.